The proposed research centers around the syntheses of an array of cyclic peptide cytochalasin analogs exploiting a novel, diastereoselective, silicon-tethered Diels-Alder cycloaddition toward the construction of the isoindolone core unit prevalent in this family of natural products. The facile approach to the cytochalasin skeleton provides the base for cytochalasin library synthesis. To prove the efficacy of this methodology, the core scaffold will initially be manipulated toward the known bioactive agent, cytochalasin B. It will be the ultimate goal of this research to utilize the core structure toward the production of novel cyclic peptide cytochalasin analogs using a diversity oriented approach. The molecules produced have the ability to serve as probes into cytochalasin-cell membrane interactions as well as have potential as biologically important compounds in areas such as cancer and AIDS research. This method also displays synthetic convergence, as a myriad of cytochalasin scaffolds can be generated from a single core unit. Finally, this research is amenable to the solid phase, which will be exploited in a cytochalasin library synthesis utilizing a ring-closing olefin metathesis cyclorelease strategy. [unreadable] [unreadable]